Sulfa Drugs: Definition, Functions, and Importance

Sulfa Drugs: Sulfonamide is a functional group (a portion of a molecule) that serves as the base for many drug classes known as sulfa drugs, sulphonamides, or sulpha drugs. Synthetic (non antibiotic) antimicrobial agents containing the sulfonamide group were the first antibacterial sulfonamides.

Few sulfonamides, such as the anticonvulsant sultiame, have no antibacterial function. Thiazide and Sulfonylureas diuretics are two newer drug classes focused on sulfonamide antibacterials.

Sulfonamide allergies are normal. Since the average rate of adverse drug reactions to sulfa antibiotics is about 3%, equivalent to penicillin, drugs including sulfonamides should be avoided.

The first widely effective antibacterials that will be used systemically were sulfonamide medicines, which laid the groundwork for the antibiotic revolution throughout medicine.

Sulfonamide Structure:

Below given diagram below represents the Sulfonamide structure:

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Classification of Sulfonamides:

Depending on the chemical composition, sulfonamide drugs are considered to be divided into two categories. Antibiotic drugs are by far the most popular. They stop bacteria from spreading (bacteriostatic), but they wouldn't destroy the ones that are already there. Trimethoprim, a bactericidal agent, is often mixed with sulfonamides.

Antibacterial effects are not found in other forms of sulfonamides. Carbonic anhydrase inhibitors (CAIs), cyclooxygenase 2 (COX-2) inhibitors, loop diuretics, thiazide diuretics, and sulfonylureas are the different types of diuretics.

• CA inhibitors are mainly used to treat glaucoma (inflammation of the optic nerve in the eye) by lowering intraocular fluid pressure.

• Another sulfonamide, zonisamide, is a CA inhibitor that is often preferred for treating seizures. The exact mechanism of zonisamide's action is still unknown.

• Thiazide diuretics have been used to cure hypertension (high blood pressure). They induce diuresis, or excessive urination, which helps reduce blood pressure. Loop diuretics, on the other hand, have been used to treat hypertension caused by heart failure. They trigger diuresis as well, but not in the same way as thiazide diuretics.

• COX-2 inhibitors are a kind of non-steroidal anti-inflammatory drug that works by affecting the COX-2 enzymes throughout the body, which are accountable for pain and inflammation symptoms.

• Type 2 diabetes is treated with sulfonylureas. They instruct the pancreas to produce additional insulin, which helps to lower blood sugar levels in the body.

Functions:

• Antibacterial sulfonamides suppress the enzyme dihydropteroate synthase (DHPS), which is included in folate synthesis in bacteria, by acting as competitive inhibitors. Sulfonamides too are bacteriostatic, inhibiting bacteria's production and replication but not killing them. 

• Humans, unlike bacteria, derive folate (vitamin B9) from their food. Sulfonamides have antifungal and antimalarial properties that are involved in treating allergies and cough.

• Other non-antimicrobial drugs which contain the moiety include thiazide diuretics (such as metolazone, hydrochlorothiazide, and indapamide), acetazolamide, loop diuretics (such as bumetanide, furosemide, and torsemide), sulfonylureas (such as glyburide and glipizide), and certain COX-2 inhibitors (for example, celecoxib).

• In comparison to being an antibiotic, sulfasalazine can also be used to cure inflammatory bowel disease.

History:

The first widely active antibacterials that can be used systemically were sulfonamide medicines, which opened the way for the antibiotic revolution in medicine. Prontosil was the very first sulfonamide, and it was a prodrug. Studies with Prontosil actually started in 1932 in the Bayer AG laboratories, which were then part of the massive German chemical conglomerate IG Farben.

Coal-tar dyes that bind selectively to bacteria and parasites, according to the Bayer team, could have been used to destroy pathogenic substances in the body.

With years of futile trial-and-error research over hundreds of dyes, a group coached by physician/researcher Gerhard Domagk finally discovered one that did work: a red dye produced by Bayer chemist Josef Klarer which had a significant effect on preventing certain infectious (bacterial) diseases in mice. The first public announcement of the groundbreaking discovery wasn't really made until 1935, upwards of two years following Klarer and his research partner Fritz Mietzsch had patented the compound.

Prontosil, as the new medication was called by Bayer, is the first drug to successfully treat a number of bacterial infections within the body. This has a powerful beneficial effect against streptococci infections, such as childbed fever, blood infections, and erysipelas, and it had a lower impact against infections that were caused by several other cocci.

It had no impact throughout the test tube, but mostly in live animals did it have an antibacterial effect. The substance was eventually revealed to be metabolized into two parts within the body, with the inactive dye part producing a smaller, colourless active compound termed sulfanilamide from the inactive dye section.

Preparation:

The reaction of a sulfonyl chloride with ammonia or an amine produces sulfonamides. Trimethoprim, a drug that inhibits dihydrofolate reductase, is often combined with other sulfonamides (sulfamethoxazole or sulfadiazine). In 2013, the Republic of Ireland was the biggest exporter of sulfonamides in the world, responsible for nearly 32% of total exports.

Side-Effects:

• Sulfonamides can produce a number of side effects, such as hematopoietic disorders, porphyria, urinary tract problems, and hypersensitivity reactions. They can cause a severe allergic reaction once taken in excess but can be cured by sulfa antibiotics.

• The Stevens-Johnson syndrome, the DRESS syndrome, toxic epidermal necrolysis (often recognized as Lyell syndrome), and a less severe SCARs reaction, acute generalized exanthematous pustulosis, are among the most serious. 

• Some sulfonamides have the ability to trigger some of these SCARs. 

• When diagnosed with sulfonamide antimicrobials, about 3% of the population in general experiences side effects. The fact that HIV patients have had a significantly higher prevalence, around 60%, is noteworthy.

• Non-Antibiotic sulfonamides cause fewer hypersensitivity reactions, and the known information indicates that those who are hypersensitive to sulfonamide antibiotics are not at an elevated risk of hypersensitivity to nonantibiotic sulfonamides.

• The arylamine group at N4 in sulfamethoxazole, sulfadiazine, sulfasalazine, and the antiretrovirals amprenavir and fosamprenavir is indeed a major aspect of the allergic reaction to sulfonamide antibiotics.

• Certain sulfonamide drugs don't really include the arylamine group; existing data indicates that patients allergic to arylamine sulfonamides need not react to sulfonamides which do not comprise the arylamine group, and thus can easily take non-arylamine sulfonamides.

• As a result, this has been proposed also that the words "sulfonamide allergy" and "sulfa allergy" be substituted with a reference to a particular drug (for example, "cotrimoxazole allergy").